Conjugates of Proteins and Multivalent Cell-Penetrating Peptides and Their Uses

Abstract

The present invention relates to conjugates comprising a protein and multivalent cell-penetrating peptide(s), each multivalent cell-penetrating peptide comprising at least two cell-penetrating peptides, wherein the multivalent cell-penetrating peptide(s) is / are covalently attached to the protein. The present invention furthermore relates to a method of generating the conjugates and to their medical uses, in particular their use in the diagnosis, prevention and / or treatment of diseases. The present invention relates to methods of diagnosis, prevention and / or treatment of diseases, comprising administering the conjugates of the invention to a patient.

Description

[0001]The present invention relates to conjugates comprising a protein and multivalent cell-penetrating peptide(s), each multivalent cell-penetrating peptide comprising at least two cell-penetrating peptides, wherein the multivalent cell-penetrating peptide(s) is / are covalently attached to the protein. The present invention furthermore relates to a method of generating the conjugates and to their medical uses, in particular their use in the diagnosis, prevention and / or treatment of diseases. The present invention relates to methods of diagnosis, prevention and / or treatment of diseases, comprising administering the conjugates of the invention to a patient.BACKGROUND OF THE INVENTION[0002]The application of novel biological therapeutics based on molecular medicine knowledge is often complicated by the large size of these compounds. Most biological therapeutics with a pronounced specificity, such as antibodies, possess a high molecular weight, but which results in unfavourable pharmaco...

AI Technical Summary

Benefits of technology

[0050]“Cell-penetrating peptides” (CPPs) refer to short peptides of 5 to 40 amino acids in length that facilitate cellular uptake of various cargoes, from nanosized particles to small chemical molecules and macromolecules, such as nucleic acids, peptides, proteins, drugs, liposomes etc. The “cargo” is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions. The attachment of one or multiple CPPs to the cargo facilitates the delivery of the cargo into cells.

[0173]More generally, the method described increases the specificity of tumor uptake of antibodies and thus provides the basis to reduce the side effects.

Problems solved by technology

The application of novel biological therapeutics based on molecular medicine knowledge is often complicated by the large size of these compounds.

Most biological therapeutics with a pronounced specificity, such as antibodies, possess a high molecular weight, but which results in unfavourable pharmacokinetic qualities setting hurdles for their clinical applications.

The successful clinical application of many high molecular weight drugs is hampered by their inability to efficiently bind to their target cell surfaces and / or traverse the cellular membrane (Sarko et al., 2010).

Solid tumors are usually slow in growth and thus successful treatment remains a challenge.

Especially, as full size antibodies have poor pharmacokinetic properties, i.e. slow binding kinetics and poor clearance, which results in collateral radiation-based damage (Song & Sgouros, 2011; Pouget et al., 2011), their usage in radioimmunodetection (RAID) and RAIT of cancer is limited.

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